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LETTER TO EDITOR
Year : 2019  |  Volume : 20  |  Issue : 1  |  Page : 91-92

A case of congenital hemangioma treated with topical timolol


Department of Dermatology, DermaClinix, New Delhi, India

Date of Web Publication14-Dec-2018

Correspondence Address:
Dr. Kavish Chouhan
DermaClinix, E 13 Defence Colony, New Delhi - 110 024
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijpd.IJPD_131_17

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How to cite this article:
Chouhan K, Kota RS, Kumar A, Gupta J. A case of congenital hemangioma treated with topical timolol. Indian J Paediatr Dermatol 2019;20:91-2

How to cite this URL:
Chouhan K, Kota RS, Kumar A, Gupta J. A case of congenital hemangioma treated with topical timolol. Indian J Paediatr Dermatol [serial online] 2019 [cited 2019 Jul 22];20:91-2. Available from: http://www.ijpd.in/text.asp?2019/20/1/91/247545



Sir,

Infantile hemangiomas (IHs) are neoplastic proliferations of endothelial cells affecting approximately 4% of the children in this age group. An imbalance between the expression of angiogenic and antiangiogenic factors has been proposed.[1] Although most hemangiomas regress on their own, they may leave residual findings such as de- or hyperpigmentation, excess skin, destruction, or a scar.[2]

A 9-month-old girl child presented to our outpatient department with red swelling over the left side of the nose which had first appeared at the age of 2 weeks and had been increasing in size since then. There was no history of bleeding or ulceration over the lesion. On examination, there was a bright erythematous swelling measuring 1.5 cm × 1.5 cm over the left side of the nose, inferomedial to medial epicanthus of the left eye [Figure 1]. The patient was clinically diagnosed to have IH. Despite of reassurance of spontaneous regression of the lesion, parents were seeking active intervention. Investigations were carried out to rule out syndromic associations such as PHACES (posterior fossa defects, hemangioma, arterial anomalies, cardiac defects, coarctation of aorta, eye anomalies, sternal clefting, and supraumbilical raphae). Investigations included routine blood investigations, blood sugar levels, chest radiography, echocardiogram, ultrasound scan of the abdomen, and magnetic resonance imaging of the brain which were normal. Timolol maleate 0.5% ophthalmic solution was prescribed, to be applied two drops twice a day on the lesion. On the first day of treatment, the patient was admitted and her vitals and blood sugars were monitored. They were also monitored on every follow-up visit once in 2 weeks. There were marked improvement, 30% resolution in 1 month, and 70% resolution in 6 months, and then, the patient was lost to follow-up. Parents have continued treatment until complete resolution which took 6 more months [Figure 2], and no side effects were observed. The patient came to follow-up at the age of 3 years with no sign of hemangioma.
Figure 1: A bright erythematous swelling measuring 1.5 cm × 1.5 cm over the left side of the nose

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Figure 2: Complete resolution of hemangioma at the age of 3 years

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IHs are most common soft tissue tumors of infancy with more than 50% of them occur in the head and neck region.[3] Prematurity and chorionic villus sampling increase its incidence.[1] There are three phases in the growth which include the phase of proliferation, starting in the 1st weeks of life and continuing over the 1st months, the phase of early involution, starting after the first year of life and continuing over the next years, and the phase of late involution, taking place around adolescence.[2]

Local complications such as ulceration, hemorrhage, and necrosis which lead to scars can occur.[4] Hemangiomas can lead to deformities when they are located on the lip, nasal tip, or ear.[2] Though active nonintervention was gold standard in case of small hemangiomas, a therapy should be indicated since no reliable factors exist that help to predict the duration of the proliferative phase. The involution phase is very slow, and there are residual findings in one-third of the cases. Furthermore, the cosmetic disfigurement caused in prominent exposed places such as face is cause of concern to the parents.[2]

Many treatment modalities have been used including topical, intralesional, and systemic corticosteroids, interferons, vincristine, imiquimod, interventional therapies such as cryotherapy, argon, neodymium-doped yttrium aluminum garnet, flashlamp-pumped pulsed dye laser, embolization, sclerotherapy, surgery, and radiotherapy. Due to the many side effects and cost factor associated with these, safer and topical modalities are now being tried in IH, especially in uncomplicated, superficial hemangiomas.[1]

Action of beta-blockers on growing IH is by three molecular mechanisms, namely, vasoconstriction, inhibition of angiogenesis (reduced expression of vascular endothelial growth factor, basic fibroblast growth factor, hypoxia-inducible factor-1, matrix metalloproteinase), and induction of apoptosis.[5] Immediate initial effect is by vasoconstriction, noticed from the 3rd day onward. Later, it aids in apoptosis, leading to involution of hemangiomas.[6]

Starting treatment in proliferative phase gives most satisfactory result.[7] Yu et al. noted that treatment with timolol before the age of 6 months had higher lesion regression rates than treatment between 6 and 12 months.[8] Topical timolol can be used in both complicated and uncomplicated hemangiomas with an efficacy similar to the systemic beta-blocker, propranolol.[1]

Major systemic side effects of timolol include bradycardia, hypotension, bronchospasm, peripheral vasoconstriction, weakness and fatigue, sleep disturbance, and hypoglycemia while pruritus is a rare cutaneous side effect.[5] Systemic absorption is highly unlikely from transdermal absorption, even when compared to ophthalmic administration.[9] Proper monitoring before and during treatment with topical timolol is required especially when used over large areas.

A large cohort study by Püttgen et al. showed that topical timolol maleate is a well-tolerated alternative to oral propranolol for selected hemangiomas, especially thin, superficial hemangiomas.[10] Danarti et al. compared efficacy of timolol maleate 0.5% solution, timolol maleate 0.5% gel, and ultrapotent corticosteroid in reducing size of IH and concluded that timolol maleate was efficacious. They found no significant differences between timolol maleate solution and gel.[11] There are several advantages with timolol such as its cost, availability, ease of administration, and minimal risk of systemic side effects.[9]

To conclude, topical timolol is an effective therapy option for IHs.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Bhat YJ, Yaseen A, Hassan I. Topical timolol maleate: An effectual and safe recourse for infantile hemangiomas. Indian Dermatol Online J 2016;7:124-5.  Back to cited text no. 1
[PUBMED]  [Full text]  
2.
Weissenstein A, Straeter A, Villalon G, Bittmann S. Topical timolol for small infantile hemangioma: A new therapy option. Turk J Pediatr 2012;54:156-8.  Back to cited text no. 2
    
3.
Re Miller T, Frieden IJ. Vascular tumours. In: Wolff K, Goldsmith LA, Katz SI, Gilchrest BA, Paller AS, Leffell DJ, editors. Fitzpatrick's Dermatology in General Medicine. 7th ed. New York: McGraw-Hill; 2008.  Back to cited text no. 3
    
4.
Khan ZA, Boscolo E, Picard A, Psutka S, Melero-Martin JM, Bartch TC, et al. Multipotential stem cells recapitulate human infantile hemangioma in immunodeficient mice. J Clin Invest 2008;118:2592-9.  Back to cited text no. 4
    
5.
Thomas J, Kumar P, Kumar DD. Ulcerated infantile haemangioma of buttock successfully treated with topical timolol. J Cutan Aesthet Surg 2013;6:168-9.  Back to cited text no. 5
[PUBMED]  [Full text]  
6.
Ambika H, Sujatha C, Kumar YH. Topical timolol: A safer alternative for complicated and un-complicated infantile hemangiomas. Indian J Dermatol 2013;58:330.  Back to cited text no. 6
[PUBMED]  [Full text]  
7.
Painter SL, Hildebrand GD. Review of topical beta blockers as treatment for infantile hemangiomas. Surv Ophthalmol 2016;61:51-8.  Back to cited text no. 7
    
8.
Yu L, Li S, Su B, Liu Z, Fang J, Zhu L, et al. Treatment of superficial infantile hemangiomas with timolol: Evaluation of short-term efficacy and safety in infants. Exp Ther Med 2013;6:388-90.  Back to cited text no. 8
    
9.
George A, Williams A. Topical timolol ophthalmic solution causing remarkable improvement in an ulcerated facial hemangioma. Indian J Paediatr Dermatol 2015;16:230-2.  Back to cited text no. 9
  [Full text]  
10.
Püttgen K, Lucky A, Adams D, Pope E, McCuaig C, Powell J, et al. Topical timolol maleate treatment of infantile hemangiomas. Pediatrics 2016;138. pii: e20160355.  Back to cited text no. 10
    
11.
Danarti R, Ariwibowo L, Radiono S, Budiyanto A. Topical timolol maleate 0.5% for infantile hemangioma: Its effectiveness compared to ultrapotent topical corticosteroids – A single-center experience of 278 cases. Dermatology 2016;232:566-71.  Back to cited text no. 11
    


    Figures

  [Figure 1], [Figure 2]



 

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